The work which we propose to do divides into four separate research projects, although three are aimed at a common goal: synthesis of biologically active alkaloids. These are: (a) continuation in the studies of the regioselectivity and mechanism of the asymmetric addition reactions of chiral sulfinylallyl anions and allylphosphonyl anions with enones, and the subsequent cyclizations to produce chiral indolizidines, pyrrolizidines, (+)-trianthine, (-)zephyranthine, (-)-dihydrolycorine, and terpenoids; (b) asymmetric alkylation reactions of alpha-amino carbanions and the subsequent ring closure reactions, and the syntheses of retronecine and indicine N-oxide; (c) synthesis of chiral pumiliotoxin alkaloids; and (d) continuation in the determination of antitumor activities of trichothecenes, synthetic intermediates and alkaloids. The first three projects aim mainly at the synthesis of biologically active alkaloids, and the chemistry are related. Our long term goals will be the extension of these works into the syntheses of chiral, naturally occurring inolizidine, pyrrolizidine, lycopodine, ibophyllidine, quinolizidine, and lycorane alkaloids. The syntheses of these alkaloids' skeletons have been proposed. The synthesized natural products and their synthetic intermediates and analogs will be tested for antitumor activity using in vitro tissue culture systems. Once the active compounds are identified, they will be tested in vivo animal models at Dr. Matthew Suffness's laboratory, Division of Cancer Treatment, NCI or Dr. Dolores Takemoto's (Co-investigator) laboratory.